Uterine smooth muscle tumor analysis by comparative genomic hybridization: a useful diagnostic tool in challenging lesions

Croce, Sabrina; Ribeiro, Agnès; Brulard, Céline; Noël, Jean‐Christophe; Amant, Frédéric; Stoeckle, Eberhard; Devouassoux-Shisheborah, Mojgan; Floquet, Anne; Arnould́, Laurent; Guyon, Frédéric; Mishellany, Florence; Garbay, Delphine; Cuppens, Tine; Zikán, Michal; Leroux, Agnès; Frouin, Éric; Duvillard, P.; Terrier, Philippe; Farré, Isabelle; Valo, Isabelle; MacGrogan, Gaëtan; Chibon, Fréderic

doi:10.1038/modpathol.2015.3

Cited by 66 publications

(51 citation statements)

References 21 publications

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“…In a recent multicenter European study, which included cases from 12 tertiary centers in France, Belgium, and the Czech Republic, 29 cases with an initial diagnosis of uterine STUMP were centrally reviewed by 2 gynecopathologists, and full agreement was obtained in only 7 (24.1%) of 29 cases. 9 The remaining cases were reported as LMS (n = 5) and benign leiomyoma variants (n = 17) after slide review. The discrepancy was due to the appreciation of the necrosis type (hyaline versus TCN) in 16 of 22 cases and the extent (focal or diffuse) and degree of nuclear atypia in the remaining 6 of 22 cases.…”

Section: Discussionmentioning

confidence: 99%

“…In a European multicenter study, 9 array comparative genomic hybridization analysis allowed discriminating between STUMPs having scarce chromosomal alterations, akin to benign leiomyomas, and STUMPs with extensive chromosomal modifications similar to LMSs. The investigators showed that STUMPs with a relatively higher genomic index had more recurrences and unfavorable outcomes.…”

Section: Discussionmentioning

confidence: 99%

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The Clinicopathological Study of 21 Cases With Uterine Smooth Muscle Tumors of Uncertain Malignant Potential

Başaran

Usubütün

Salman

et al. 2018

International Journal of Gynecological Cancer

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Clinicopathological Study of 21 Cases With Uterine Smooth Muscle Tumors of Uncertain Malignant Potential

Başaran

Usubütün

Salman

et al. 2018

International Journal of Gynecological Cancer

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“…Seventy-seven formalin-fixed and paraffinembedded uterine smooth muscle lesions from 76 patients (for one patient, both the primary tumor and the recurrence were examined) were collected in France through the French sarcoma network ( 17 were included in the series. The tumors were diagnosed between 1977 and 2013.…”

Section: Tumor Samplesmentioning

confidence: 99%

“…A few years ago, we published a new classification method based on genomic profiling complementary to the morphology able to distinguish within the STUMP category those uterine smooth muscle lesions with a risk of recurrence and poor outcomes from benign lesions. 17 In this study, we analyzed the genomic profile by array-comparative genomic hybridization in a series of 77 uterine smooth muscle lesions (44 leiomyosarcomas, 14 STUMP and 19 leiomyomas) to validate the power of genomic index as a recurrence predictor. Furthermore, we set out to improve our previous results by studying a larger series with a broader follow-up and to identify overall survival prognostic factors in uterine leiomyosarcomas.…”

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confidence: 99%

Genome profiling is an efficient tool to avoid the STUMP classification of uterine smooth muscle lesions: a comprehensive array-genomic hybridization analysis of 77 tumors

Croce¹,

Ducoulombier²,

Ribeiro³

et al. 2018

Modern Pathology

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The diagnosis of a uterine smooth muscle lesion is, in the majority of cases, straightforward. However, in a small number of cases, the morphological criteria used in such lesions cannot differentiate with certainty a benign from a malignant lesion and a diagnosis of smooth muscle tumor with uncertain malignant potential (STUMP) is made. Uterine leiomyosarcomas are often easy to diagnose but it is difficult or even impossible to identify a prognostic factor at the moment of the diagnosis with the exception of the stage. We hypothesize, for uterine smooth muscle lesions, that there is a gradient of genomic complexity that correlates to outcome. We first tested this hypothesis on STUMP lesions in a previous study and demonstrated that this 'gray category' could be split according to genomic index into two groups. A benign group, with a low to moderate alteration rate without recurrence and a malignant group, with a highly rearranged profile akin to uterine leiomyosarcomas. Here, we analyzed a large series of 77 uterine smooth muscle lesions (from 76 patients) morphologically classified as 19 leiomyomas, 14 STUMP and 44 leiomyosarcomas with clinicopathological and genomic correlations. We confirmed that genomic index with a cut-off=10 is a predictor of recurrence (P<0.0001) and with a cut-off=35 is a marker for poor overall survival (P=0.035). For the tumors confined to the uterus, stage as a prognostic factor was not useful in survival prediction. At stage I, among the tumors reclassified as molecular leiomyosarcomas (ie, genomic index ≥10), the poor prognostic markers were: 5p gain (overall survival P=0.0008), genomic index at cut-off=35 (overall survival P=0.0193), 13p loss including RB1 (overall survival P=0.0096) and 17p gain including MYOCD gain (overall survival P=0.0425). Based on these findings (and the feasibility of genomic profiling by array-comparative genomic hybridization), genomic index, 5p and 17p gains prognostic value could be evaluated in future prospective chemotherapy trials.

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“…Tumors short on these criteria are diagnosed as smooth muscle tumors of uncertain malignant potential. 6,26,27 Molecular data are available for uterine spindle cell leiomyosarcomas and leiomyosarcomas in soft tissues demonstrating variable cytogenetically complex numerical and structural changes of tumors, highlighting the degree of genomic instability. 28,29 Frequent loss of heterozygosity particularly for chromosomes 10 and 13 has been described.…”

Section: Introductionmentioning

confidence: 99%

Exploring chromosomal abnormalities and genetic changes in uterine smooth muscle tumors

et al. 2016

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Smooth muscle tumors of the uterus are a diagnostically challenging group of tumors. Molecular surrogate markers reliably distinguishing between benign and malignant tumors are not available. Therefore, the diagnosis is based on morphologic criteria. The aim was to investigate a well-characterized group of challenging uterine smooth muscle tumors consisting of 20 leiomyomas, 13 leiomyomas with bizarre nuclei, and 14 leiomyosarcomas for copy number alterations, MED12 mutations and FH deletions to search for potential diagnostically useful surrogate markers. MED12 mutations were detected in 47, 15, and 25% of leiomyomas, leiomyomas with bizarre nuclei and leiomyosarcomas, respectively. MED12 mutations in leiomyomas with bizarre nuclei were detected outside the hotspot region. FH-deletions were seen in 27, 30.8, and 25% of leiomyomas, leiomyomas with bizarre nuclei and leiomyosarcomas, respectively. By using copy number alteration profiling a clear separation of leiomyomas, leiomyomas with bizarre nuclei and leiomyosarcomas could not be observed. Copy number alterations revealed clear genetic similarities between leiomyomas with bizarre nuclei and leiomyosarcomas. Leiomyosarcomas showed a similar pattern of gains and losses as leiomyomas with bizarre nuclei, with additional copy number alterations and more homozygous losses and high-level amplifications compared to leiomyomas with bizarre nuclei. In conclusion, this study demonstrates that known FH-deletions, a recurrent molecular change in leiomyomas, occur in morphologically challenging variants of leiomyomas, leiomyomas with bizarre nuclei and leiomyosarcomas. Although MED12 mutations are common in leiomyomas, they infrequently occur in leiomyomas with bizarre nuclei and leiomyosarcomas. The genetic similarities between leiomyomas with bizarre nuclei and leiomyosarcomas raise the intriguing possibility that uterine leiomyomas with bizarre nuclei and leiomyosarcomas are closely related and challenge the traditional concept that leiomyoma with bizarre nuclei is a tumor with just marked 'degenerative' cellular changes. These findings support the hypothesis that tumor progression within uterine smooth muscle tumors might occur.

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Uterine smooth muscle tumor analysis by comparative genomic hybridization: a useful diagnostic tool in challenging lesions

Cited by 66 publications

References 21 publications

The Clinicopathological Study of 21 Cases With Uterine Smooth Muscle Tumors of Uncertain Malignant Potential

The Clinicopathological Study of 21 Cases With Uterine Smooth Muscle Tumors of Uncertain Malignant Potential

Genome profiling is an efficient tool to avoid the STUMP classification of uterine smooth muscle lesions: a comprehensive array-genomic hybridization analysis of 77 tumors

Exploring chromosomal abnormalities and genetic changes in uterine smooth muscle tumors

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